Investor science event from ASH 2008 San Francisco, 9 December 2008

Transcription

1 Investor science event from ASH 2008 San Francisco, 9 December 2008

2 Forward-looking statements This presentation contains certain forward-looking statements. These forward-looking statements may be identified by words such as believes, expects, anticipates, projects, intends, should, seeks, estimates, future or similar expressions or by discussion of, among other things, strategy, goals, plans or intentions. Various factors may cause actual results to differ materially in the future from those reflected in forward-looking statements contained in this presentation, among others: 1 pricing and product initiatives of competitors; 2 legislative and regulatory developments and economic conditions; 3 delay or inability in obtaining regulatory approvals or bringing products to market; 4 fluctuations in currency exchange rates and general financial market conditions; 5 uncertainties in the discovery, development or marketing of new products or new uses of existing products, including without limitation negative results of clinical trials or research projects, unexpected side-effects of pipeline or marketed products; 6 increased government pricing pressures; 7 interruptions in production; 8 loss of or inability to obtain adequate protection for intellectual property rights; 9 litigation; 10 loss of key executives or other employees; and 11 adverse publicity and news coverage. Any statements regarding earnings per share growth is not a profit forecast and should not be interpreted to mean that Roche s earnings or earnings per share for this year or any subsequent period will necessarily match or exceed the historical published earnings or earnings per share of Roche. Please see for full information on Roche products mentioned. 2

3 Introduction Dr. Karl Mahler, Head of Investor Relations

4 Agenda MabThera/Rituxan(rituximab) in 1st line CLL 1 (CLL-8 phase III trial) Professor Michael Hallek, Department of Internal Medicine, University of Cologne, Germany MabThera/Rituxan(rituximab) in relapsed CLL (REACH phase III trial) Professor Tadeusz Robak, Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland R7159/GA101 in CD20+ malignant disease (GELA phase I trial) Professor Gilles Salles, Department of Haematology, Hospices Civils of Lyon, Head of the Research Unit Pathologie des Cellules Lymphoïdes, University of Lyon, France MabThera/Rituxan: The answer for all CD20+ disease patients Detlef Krawinkel, MabThera Life Cycle Leader, Roche Pharma Questions & Answers Total duration: Up to 1½ hour 1 CLL = Chronic Lymphocytic Leukemia 4

5 MabThera/Rituxan: Largest hematology product Top-15 products commonly used to treat hematological malignancies Global sales 1 MabThera/Rituxan Quarterly global sales Imatinib Bortezomib Doxorubicin Lenalidomide Thalidomide Dexamethasone Topotecan Dasatinib Prednisone Fludarabine Alemtuzumab Melphalan 1 Source: IMS Q4-97 Q3-98 Q2-99 Q1-00 Q4-00 Q3-01 Q2-02 Q1-03 Q4-03 Q3-04 Q2-05 Q1-06 Q4-06 Q3-07 Q2-08 Cyclophosphamide Bendamustine 5

6 MabThera/Rituxan: New uses have powered growth Roche Pharma still realizing the full RoW potential Global sales MabThera/Rituxan CHF million R/R follicular inhl mono (U.S.) R/R follicular inhl mono (EU) Follicular inhl (JP) anhl (JP) anhl in combo w/chop (EU) 1 st line inhl in combo w/cvp (EU) 1 st line anhl in combo w/chop or other anthracycline-based chemo (U.S.); 1 st line follicular inhl in combo w/cvp (U.S.); maintenance in follicular inhl (U.S.,EU); and rheumatoid arthritis anti-tnf IR in combo w/mtx (U.S., EU) US Japan RoW M M 2008 R/R = Relapsed/Refractory; inhl = indolent Non-Hodgkins Lymphoma (low grade); anhl = aggressive Non-Hodgkins Lymphoma (diffuse large B-cell lymphoma); CHOP = cyclophosphamide, doxorubicin, vincristine, prednisone; CVP = cyclophosphamide, vincristine, prednisone; anti-tnf IR = anti-tumor Necrosis Factor Inadequate Responders; MTX = methotrexate 6

7 CLL is the second-largest leukemia worldwide Incidence numbers expected to remain fairly stable Incidence of hematological malignancies Incidence of leukemia subtypes 160, , , ,000 80,000 60,000 40, ,082 8,553 10,879 12,945 9,099 11,516 26,165 27,981 Other ALL CML AML CLL 20,000 0 NHL Leukemia MDS MM HL 23,789 25, ALL = Acute Lymphocytic Leukemia; AML = Acute Myeloid Leukemia; CLL = Chronic Lymphocytic Leukemia; CML = Chronic Myeloid Leukemia Source: Datamonitor, hematological malignancies 03/2007, 12/2007; seven major markets: U.S., France, Germany, Itlay, Spain, UK, Japan 7

8 R7159/GA101: Potential for increased benefits 3rd gen. anti-cd20 molecule with distinct properties Roche's anti-cd20 antibody strategy: Designing specific molecules for specific markets R1594(ocrelizumab) 2nd gen. molecule for use in inflammation, including RA and RRMS R7159/GA101 3rd gen. molecule intended for exclusive use in hematology, including NHL and CLL Strategy intended to eventually replace MabThera/Rituxan before patent expiry during the next decade R7159/GA101 is a fully humanized and glycoengineered type II anti-cd20 monoclonal antibody Genetic engineering of CHO cell line to produce antibody glycosylation and other modifications enabling tailored antibody properties, including Enhanced induction of direct cell death Increased affinity and ADCC 1 Clinical data for MabThera/Rituxan(rituximab) and Herceptin(trastuzumab) support the hypothesis that enhancing the ADCC of the antibody may lead to higher efficacy in cancer treatment Lower CDC 2 activity Currently undergoing phase I/II trials in CD20+ hematological malignancies 1 ADCC = Antibody-Dependent Cell-mediated Cytotoxicity 2 CDC = Complement-Dependent Cytotoxicity 8

9 MabThera/Rituxan(rituximab) in 1st line CLL (CLL-8 phase III trial) Professor Michael Hallek, Department of Internal Medicine, University of Cologne, Germany

10 Rationale I: Fludarabine (F) + cyclophosphamide (C) is superior to F in Previously Untreated CLL Regimen Chl F FC F FC F FC N Med age Rai Stage III- IV, Binet C (%) Grade 3 / 4 ANC (%) % CR % OR Med PFS (mo) Catovsky D, et al. Lancet. 2007;370: ; Flinn FW, et al. J Clin Oncol. 2007;25: ; Eichhorst BF, et al. Blood. 2006;107:

11 Rationale II: improved efficacy by combining FC chemotherapy with rituximab (MD Anderson, historical comparison) Outcome n 6-year OS F % F±M/C R-FC % 77% p value p=0.37 p<0.001 Probability Time (months) Tam CS, et al. Blood 2008;112:

12 CLL8 Study Design Patients with untreated, active CLL and good physical fitness (CIRS 6, creatinine clearance 70 ml/min) R FCR FC 6 courses C1 C2 C3 C4 C5 C6 Follow up Primary endpoint -Progression-free survival (PFS) Secondary endpoints - Overall survival - Rates of molecular, complete and partial remission - Rates of treatment-related adverse effects 12

13 Patients: ITT population (n=817) of the CLL8 protocol FC (n = 409) FCR (n = 408) Female 105 (26%) 105 (26%) Male 304 (74%) 303 (74%) Median age 61 (range 36-81) 61 (range 30-80) Binet A 22 (5.4%) 18 (4.4%) Binet B 259 (63.6%) 263 (64.6%) Binet C 126 (31%) 126 (31%) B symptoms* 197 (48%) 167 (41%) Median cumulative illness rating scale (CIRS) 1 (range 0-8) 1 (range 0-7) Trisomy % 9.6% Del(13q) 59.9% 53.7% Del(11q23) 22.5% 26.7% Del(17p13) 9.5% 7.0% *P<0,05 13

14 Therapy number of courses applied FC FCR

15 All adverse events of CTC grade 3 and 4 Total number of patients with 1 grade 3/4 event FC FCR p 248 (62.6%) 309 (77.5%) < Hematological toxicity 39.4% 55.7 % < Neutropenia 21.0% 33.7% < Leukocytopenia 12.1% 24.0% < Thrombocytopenia 10.9% 7.4% 0.09 Anemia 6.8% 5.4% 0.42 Infection 14.9% 18.8% 0.14 Tumor lysis syndrome 0.5% 0.2% 0.55 Cytokine release syndrome 0.0%

16 Infectious adverse events, grade 3 and 4 FC FCR p Infections, total 14.9% 18.8% 0.14 Infections, if specified 9.3% 13.6% 0.06 Bacterial 1.3% 2.2% 0.30 Viral 4.0% 4.2% 0.90 Fungal 0.3% 0.7% 0.33 Parasitic 0.0% 0.2% 0.32 Differences not statistically significant Treatment related mortality: 2.0% in the FCR and 1.5% in the FC arm 16

17 Response to treatment FC FCR p CR 22.9% 44.5% <0. 01 CR u 5.1% 3.3% 0.22 CR i 1.9% 2.6% 0.52 npr 4.9% 2.8% 0.15 PR 50.4% 39.6% <0.01 SD 6.7% 3.9% 0.08 PD 8.1% 3.3% <

18 Progression free survival: FCR versus FC Median observation time 25.5 months p= Median PFS: 32.3 months for FC vs 42.8 months for FCR 18

19 Progression free survival according to Binet stages Binet Binet A stages A+B Binet stage C p< p=0.44 ORR 93,3% ORR 88,0% 19

20 Overall survival p=0.18 Median observation time 25.5 months 20

21 Overall survival and type of response 21

22 Conclusion: FCR first-line treatment in CLL FCR is superior to FC with regard to: Response rates (CR, OR). Progression-free survival. FCR treatment is safe: FCR causes more neutropenias FCR does not cause more infections or other severe side. FCR is well tolerated in physically fit patients > 65 or 70 years. FCR is the new standard treatment for physically fit CLL patients Data on prognostic factors and minimal residual disease assessment will be presented by Stephan Stilgenbauer (ASH # 781) and 22 Sebastian Böttcher (ASH # 326).

23 MabThera/Rituxan(rituximab) in relapsed CLL (REACH phase III trial) Professor Tadeusz Robak, Department of Hematology, Medical University of Lodz and Copernicus Memorial Hospital, Lodz, Poland

24 REACH: Study Design R-FC vs FC Relapsed / refractory CLL One previous therapy Binet A, B, C ECOG PS 0 1 FC or prior antibody therapy not allowed R A N D O M I Z E R-FC q4wk 3 FC q4wk 3 R E S T A G E R-FC q4wk 3 CR, PR, (SD) FC q4wk 3 n = sites PD off study Rituximab Fludarabine Cyclophosphamide Cycle mg/m 2 day 0 Cycles mg/m 2 day 1 25 mg/m 2 iv, day mg/m 2 iv, day 1 3 Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

25 REACH: Recruitment by Country (n=552) Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

26 REACH: Demographics and Patient Characteristics FC n = 276 R-FC n = 276 Median age (range) 62 (35 81) 63 (35 83) Female sex 34% 32% A 11% 9% Binet stage B 58% 60% C 31% 31% ECOG PS 0 59% 61% ECOG PS 1 41% 39% B symptoms 31% 26% Median creatinine clearance (ml/min) β2 microglobulin > ULN 78% 76% % are based on patients with information available for the corresponding parameter Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

27 REACH: Selected Stratification Factors FC n = 276 R-FC n = 276 Median time from first diagnosis 3.7 yrs 3.8 yrs Previous therapy Alkylator Refractory 26% 27% Sensitive 56% 55% Purine analog 17% 16% Alkylator fludarabine 1% 2% Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

28 REACH: Treatment Cycles Received %100% 95.6% 92.3% 86.8% 91.2% 76.8% 83.2% 77.4% 72.4% FC (n=272) R-FC (n=274) Patients (n) % 67.5% Cumulative No. of Cycles Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

29 REACH: Selected Grade 3/4 CTC Adverse Events Event type FC (%) n = 272 R-FC (%) n = 274 All Infusion-related (d1-2 of 1 st cycle) 4 6 Tumor Lysis Syndrome 3 2 Neutropenia Febrile Neutropenia Thrombopenia 9 11 AIHA 12 5 Infections Hepatitis B 2 Benign or Malignant Neoplasms 3 7 Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

30 REACH: Response Rates FC (%) n = 276 R-FC (%) n = 276 p CR PR/nPR ORR SD n.d. PD n.d. not evaluable* n.d. *Mainly patients with response that was not confirmed through a second assessment n.d.: not done Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

31 REACH: Primary Endpoint PFS ITT 1.0 Median follow-up 25.3 months Event-free rate 0.4 R-FC Median PFS: 30.6 months No. at risk FC R-FC p = (log-rank) HR 0.65 [0.51; 0.82] FC Median PFS: 20.6 months Months Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

32 REACH: PFS by Previous Treatment (R-FC) ITT 1.0 Median follow-up 25.3 months Event-free rate 0.4 Previous chemotherapy Alkylator refractory Alkylator sensitive Fludarabine No. at risk Alkylator refractory Alkylator sensitive Fludarabine Months Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

33 REACH Binet Subgroups PFS ITT Binet stage HR [95% CI] for PFS A (n = 55) B (n = 326) C (n = 171) 0.75 [0.33; 1.72] 0.65 [0.47; 0.88] 0.61 [0.41; 0.90] Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

34 REACH: PFS by ZAP-70, IgV H ITT ZAP-70 positive (n=173) ZAP-70 negative (n=237) Event-free rate Log-rank test p= Randomised treatment FC R-FC Event-free rate Log-rank test p= Randomised treatment FC R-FC Months Months IgV H unmutated (n=328) IgV H mutated (n=192) Event-free rate Log-rank test p= Randomised treatment FC R-FC Event-free rate Log-rank test p= Randomised treatment FC R-FC Months Months Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

35 REACH: PFS by Cytogenetics ITT del11q (n=115) Trisomy 12 (n=69) 1.0 Randomised treatment 1.0 Randomised treatment Event-free rate Log-rank test p= FC R-FC Months Event-free rate Log-rank test p= FC R-FC Months del17p (n=42) del13q (n=309) Event-free rate Log-rank test p= Randomised treatment FC R-FC Months Event-free rate Log-rank test p= Months Randomised treatment FC R-FC Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

36 REACH: Overall Survival ITT 1.0 Median follow-up 25.3 months 0.8 R-FC Median OS: not reached 0.6 Event-free rate 0.4 No. at risk FC R-FC p = (log rank) HR 0.83 [0.59;1.17] FC Median OS: 51.9 months Months Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

37 REACH Subsequent Therapy FC 69 patients relapsed and received therapy 49% received rituximab-containing regimens R-FC 47 patients relapsed and received therapy 30% received rituximab-containing regimens Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

38 REACH: Summary Rituximab plus FC is significantly superior to FC alone in relapsed / refractory CLL patients Results were robust and consistent in subgroups and across secondary endpoints, including adverse prognostic groups - Binet C -11q -unmutated IgVH, ZAP-70 positive R-FC showed a favorable risk-benefit profile with no new or unexpected safety findings Abstract LBA-1, presented at the 50 th Annual Meeting of the American Society of Hematology, San Francisco, Dec 6 9 th, 2008

39 R7159/GA101 in CD20+ malignant disease (GELA phase I trial) Professor Gilles Salles, Department of Haematology, Hospices Civils of Lyon, Head of the Research Unit Pathologie des Cellules Lymphoïdes, University of Lyon, France

40 GA101: a new anti-cd20 antibody First glycoengineered, humanized, type II CD20 antibody in clinical development Compared with rituximab, GA101 provides: Enhanced direct cell death induction 1,2 Enhanced ADCC 1,2 1. Umaña P, et al. Ann Oncol 2008; 19:Suppl 4;Abstract Umaña P, et al. Blood 2006; 108:(11 Pt 2);Abstract 229.

41 GA101: mechanisms of action Versus type I antibodies Increased direct cell death Unique type II epitope & elbow-hinge modification Increased ADCC via increased affinity to the 'ADCC receptor' FcgRIIIA Effector cell B cell CD20 Lower CDC activity Due to recognition of type II epitope FcgRIIIa Complement

42 BO20999: Trial rationale and design Monoclonal antibody therapy has markedly improved the outcome of B-cell malignancies: but there is still a need for further progress GA101 is a new anti-cd20: Modified type II, glycoengineered and humanized Preclinical data indicate superiority for ADCC and cell death BO20999 is an open-label, multicenter, phase I/II study to explore GA101 activity phase I part to investigate the safety and tolerability of GA101 given as single agent in patients with CD20+ malignant disease non-randomized and adaptive dose-escalating design

43 Study BO20999: Phase I dose-escalation (3+3 design) GA101 single agent (total 9 doses) TUMOR ASSESSMENT weeks CD20+ malignant disease for whom no therapy of higher priority was available n = 3 per cohort Successive cohorts initiated if no DLT Started in September 2007 at 7 sites in France Cohort group GA101 dose Dose 1 / doses / 100 mg 100 / 200 mg 200 / 400 mg 400 / 800 mg 800 / 1200 mg 1200 / 2000 mg 1600 / 1600 / 800 mg GA101 administered as per rituximab administration guidelines

44 GA101 Phase I: Patient characteristics Patients, n 21 Follicular lymphoma 15 Mantle cell lymphoma 3 Diffuse large B-cell lymphoma 1 Lymphocytic/lymphoplasmacytoid lymphoma 1 Waldenström s macroglobulinaemia 1 Male / Female 9 / 12 Haematological parameters Haemoglobin, median (range) 12.9 g/dl ( ) White blood count, median (range) 5.9 x 10 9 /l (3.3 80) Platelets, median (range) 191 x 10 9 /l (89 363) Prior therapies, median (range) 3 (1 7) Prior rituximab 95% Prior ASCT 52% Duration of response to last treatment, median (range) 12 mo (3 112)

45 GA101 well tolerated with preliminary safety profile very similar to rituximab Majority of toxicities grade 1 2 No grade 4 toxicities Four SAEs were observed, one related to the drug that was completely reversible (tumor lysis with thrombocytopenia and neutropenia) Infusion related reactions, mostly grade 1 & 2, more frequent around time of first infusion, less frequent with subsequent infusions: Hypotension Nausea Pyrexia Vomiting Chills Hyperthermia Arthralgia Diarrhoea

46 Analysis of overall response rate in NHL patients 21 patients NHL sub-types 15 FL 1 lymphocytic lymphoma 1 WM 1 DLBCL 3 MCL Best response (%) 4 CR, 5 PR (43%) 8 of 9 responses still ongoing ORR = 47% when only indolent lymphoma (n=17) are considered

47 GA101: Best Tumor Response (18 patients) 150 > 100% % change in indicator lesions a b Patients 150 a = PET-verified CR; b = Death; 1600 / 1600 / 800 mg cohort not included

48 Patient Story: Mantle Cell Lymphoma Patient Male Age 73 Diagnosis: Mantle Cell Lymphoma [Ann Arbor Stage IV/2003] 2 previous lines of therapy R-CHOP [PR] and FC [CR] Baseline WBC: 94x10 9 /l Lymphocyte Count: 92 x 10 9 /l Platelets: 73 x 10 9 /l Splenomegaly (25 cm below costal margin), bulky disease Cycle 1 Day 1 (1200mg): Infusion well tolerated ~ 5 hours post-infusion: Tumor lysis, thrombocytopenia (G4), neutropenia(g3) SAE WBC: 4x10 9 /l 48

49 Patient Story: Mantle Cell Lymphoma Patient Cycle 1 Day 7 WBC: 50x10 9 /l (patient in leukemic phase/re-bound of disease observed) Cycle 1 Day 8 (2000mg) - WBC: 4x10 9 /l and patient feeling very well Cycle 3 Day 1/Patient s disease under control WBC: 2.2x10 9 /l lymphocytes 0.48x10 9 /l platelets 110 x 10 9 /l (spontaneous recovery of platelets) (Spleen 6cm below costal margin and patient feeling very well) Patient received all 9 infusions - Spleen now normal size, WBC and platelets remain normalized - Best response to GA101 = PR GA101 effective as single agent in treatment of MCL patient Patient s quality of live dramatically improved 49

50 Conclusions Safety profile: GA101 is well tolerated with no dose-limiting toxicities very similar to that of rituximab Preliminary PK data suggest that baseline tumor burden is an important co-variate Encouraging efficacy observed in relapsed/ refractory NHL patients: B-CLL data pending (12 patients) Phase II study enrolling indolent and aggressive NHL

51 MabThera/Rituxan: The answer for all CD20+ disease patients Detlef Krawinkel, MabThera Life Cycle Leader, Roche Pharma

52 MabThera/Rituxan: Current status & strategy The new standard of care in CLL Further maintenance indications, ITP, and lifecycle strategy 52

53 MabThera/Rituxan: The success continues Group sales (CHF bn) US Japan RoW Outstanding clinical data and extensive development program Overall survival benefit combined with excellent tolerability Large randomized clinical trials support further registrations: CLL 1 st line CLL relapsed inhl 1 st line maintenance Others Over 1.5 million patients treated

54 Widely utilized in NHL 1 st /2 nd line while CLL and maintenance indications are future growth drivers Depth in core CD-20+ indications inhl 1 st line maintenance Growth drivers, shorter term Growth drivers, longer term Already-launched NHL indications anhl & CLL maintenance CLL Others Breadth in hematology 54

55 Penetration rates validate the opportunities in CLL and further maintenance indications Split of global sales Penetration rates Q Japan 3% Key 5 EU inhl 1st line maintenance 17 % RoW 45% CLL 1 st line 26 % inhl relapsed maintenance 33 % CLL relapsed 38 % US 52% anhl relapsed 64 % inhl relapsed 67 % 2007 CHF 5.5 bn inhl 1 st line 72 % anhl 1 st line 84 % Source: Roche market research Q Note: CLL and maintenance therapy in 1 st line indolent NHL are non-approved indications in EU/RoW 55

56 MabThera/Rituxan Four drivers for continued sales growth in oncology 1. CLL 1 st line and relapsed 2. Expand and prolong treatment (maintenance) 3. Introduce MabThera/Rituxan s.c. as new SoC in maintenance 4. Increase penetration and dosage s.c. = sub-cutaneous; SoC = Standard of Care 56

57 MabThera/Rituxan: Current status & strategy The new standard of care in CLL Further maintenance indications, ITP, and lifecycle strategy 57

58 CLL completes the picture and makes MabThera/Rituxan the answer for all CD20+ patients Typical patient split & EU indications inhl 1 st line 22% 15% inhl relapsed Approval expected 2009 CLL relapsed CLL 1 st line 9% 10% 29% anhl 1 st line 15% anhl relapsed 58

59 Large extension of life free from disease progression CLL 1st line and relapsed/refractory patients CLL8 1 1st line patients REACH 2 relapsed patients 1.0 Randomised treatment FC FCR 1.0 Randomised treatment FC FCR Event HR 0.56 p= FC-R: Median 40 months FC: Median 32 months Progression-free rate HR 0.65 p = FC: Median 20.6 months FC-R: Median 30.6 months ,001 1,092 1,183 1,274 1,365 1,456 Days Time (years) MabThera/Rituxan-chemo vs chemo alone significantly improved PFS in both CLL 1 st line and relapsed/refractory FC = fludarabine, cyclophosphamide; FC-R = fludarabine, cyclophosphamide + MabThera/Rituxan 1 ASH 2008 Abstract 325. Hallek et al. 2 ASH 2008 Abstract (late breaker). Robak et al. 59

60 MabThera/Rituxan: New standard of care in CLL Treatable CLL patients per year (top 5 EU) ~17,000 (which compares to ~50% of the number of treatable patients with inhl) 1st line treatment choice Future MabThera/Rituxan + chemotherapy ~8,500 patients Current Immuno or immunochemotherapy 30% of patients Chemotherapy 70% of patients Relapsed treatment choice Future MabThera/Rituxan + chemotherapy ~8,500 patients Current Immuno or immuno-chemotherapy 50% of patients Chemotherapy 50% of patients Source: Patient case market research Q2 2008; values are rounded 60

61 MabThera/Rituxan: Current status & strategy The new standard of care in CLL Further maintenance indications, ITP, and lifecycle strategy 61

62 MabThera/Rituxan is expected to become standard of care in further indications Ongoing phase III trials inhl 1st line maintenance Trial, study group, PE, time Treatment Patients (EU) PRIMA GELA, France PFS 2011 R-CHOP/CVP-> 2 yrs R maintenance vs. R- CHOP/CVP -> observation 11,500 Rituxan anhl 1st line maintenance NHL 13 trial AGMT, Austria EFS 2012 R-chemo -> 2 yrs R maintenance vs. observation 24,000 CLL maintenance GOELAMS and FCGCLL/WM -, France PFS 2012 R-FC -> 2 yrs R maintenance vs. observation 15,000 Rituxan + Avastin anhl 1st line induction MAIN, Roche-sponsored PFS 2012 R-CHOP vs. Avastin-R- CHOP induction 25,400 62

63 Maintenance treatment in CD20+ hematological malignancies: A very large untapped potential Typical patient split & EU indications Potential approval 2012 CLL 17% anhl 39% 16% inhl relapsed, the only approved EU indication Potential approval % inhl 1 st line 63

64 S.c. formulation will be developed to fully explore the potential in maintenance treatment Formulation will have all the current benefits of MabThera/Rituxan Additional benefits for patients, payers and prescribers Possibility of non-hospital/self administration Improved patient convenience and preference greater independence Less resource-intensive than i.v. administration Reduced medical resource utilization (address capacity issues) Maximizing the overall Roche hematology franchise value 64

65 MabThera/Rituxan: Potential in non-oncological hematology - example First to report randomized data for MabThera/Rituxan-treated ITP 1 patients Treatable patients in EU are around 13,000 Dexamethasone MabThera/Rituxan + dexamethasone p-value n ITT platelet count (%) 50 x 10 9 /l PP platelet count (%) 50 x 10 9 /l ITP = Idiopathic Thrombocytopenic Purpura; ITT = Intent-To-Treat population; PP = Per Protocol population Abstract 1. Session: Lymphoma: Chemotherapy and Clinical Trials Poster II Zaja et al. Sun 7 Dec 2:00 PM. Moscone Center, Halls B & C 65

66 Roche in hematology: More opportunities Phase I Phase II Phase III Registration R7112 R7159 GEN GEN oncology NHL anti-cd20 3rd gen. hem. malig. ABT-263 solid tumors & hem. malig. GEN GEN GEN CD40 Ab diff. large B Cell lymph. Apomab - cancer Apo2L/TRAIL - cancer R105 R105 R105 MabThera CLL relapsed MabThera inhl maint. 1 st line MabThera + Avastin NHL aggr. R105 MabThera CLL 1 st line GEN CD40 Ab NHL/MM/rel.large B-CL NME Additional Indications DBA Oncology R-No. GEN Roche managed Genentech managed Status as of 30 September

67 Questions & Answers Moderator: Dr. Karl Mahler, Head of Investor Relations

68 We Innovate Healthcare 68